Blistering skin disorders (pemphigus, bullous pemphigoid, dermatitis herpetiformis)

1. Terminology

• Blister = common term for vesicle and bulla.
• Vesicle: fluid-filled raised area ≤ 5 mm.
• Bulla: fluid-filled raised area > 5 mm (large vesicle).

2. Pemphigus (Vesiculobullous Pattern)

Definition

• Autoimmune disorder: loss of integrity between cells in epidermis + mucosal epithelium.
• Due to autoimmune destruction of desmosomes.
• Middle-aged or older, usually females.

Three Major Variants

• Pemphigus vulgaris (most common).
• Pemphigus foliaceus.
• Paraneoplastic pemphigus (associated with internal malignancy).

Pathogenesis

• Type II hypersensitivity reaction (vulgaris + foliaceus).
• IgG autoantibodies against desmoglein 1 + 3 (desmosomal proteins).
• Antibodies attack desmoglein → anchoring lost → skin/mucous membrane “unzips” → fluid gathers → blister.

Pemphigus Vulgaris

• Most common variant.
• Involves mucosa + skin (scalp, face, axilla, groin).
• Suprabasal blisters → superficial painful flaccid blisters that rupture easily → erosions covered by crusts.
• ⁺ Nikolsky sign (lateral pressure → skin slides off).
• Desmoglein 3 (± 1).

Pemphigus Foliaceus

• More rare, benign form, only skin (no mucosa).
• Blisters very superficial (stratum granulosum) → only erosions / crust visible.
• Desmoglein 1.

Direct Immunofluorescence (DIF)

• “Fishnet” / chicken-wire intercellular IgG deposition between keratinocytes.

3. Bullous Pemphigoid (Vesiculobullous Pattern)

Definition

• Middle-aged + older, usually males.
• Autoimmune: IgG + complement linearly deposited at basement membrane.
• Due to autoimmune destruction of hemidesmosomes (basal cell-BM attachment).
• Antigens: BP180 (collagen XVII) + BP230.
• Tissue injury by recruited neutrophils + eosinophils.

Morphology

• Subepidermal blisters → “roof” = intact epidermis → more resistant to rupture than pemphigus blister (tense).

Clinical Features

• Tense bullae filled with clear fluid on normal/erythematous skin.
• If uncomplicated by infection → healing without scarring.
• Sites: inner thighs, flexor surfaces of forearms, axilla, groin, lower abdomen.
• Nikolsky sign negative.
• No mucosal involvement (usually).

DIF

• Linear IgG + C3 at basement membrane.

4. Dermatitis Herpetiformis

Definition

• Rare disorder of intensely itchy blisters with watery fluid.
• Often affects males in 3rd–4th decades.

Pathogenesis

• Strong association with celiac disease; responds to gluten-free diet.
• Genetically predisposed individuals develop IgA antibodies against gluten (gliadin).
• Antibodies cross-react with reticulin / tissue transglutaminase — anchoring fibrils binding BM to dermis.
• Injury + inflammation → subepidermal blister.

Morphology

• Subepidermal blisters.
• Basal cells show vacuolization + focal dermo-epidermal separation.
• Neutrophils accumulate at tips of dermal papillae (microabscesses).

Clinical Features

• Lesions are extremely itchy, bilateral, symmetric.
• Sites: extensor surfaces (elbows, knees), upper back, buttocks.
• HLA-DQ2 / DQ8.

DIF

• Granular IgA deposits at tips of dermal papillae (pathognomonic).

5. Comparison Table

Feature	Pemphigus vulgaris	Bullous pemphigoid	Dermatitis herpetiformis
Age/Sex	Middle-aged, female	Older, male	30s–40s, male
Antibody	IgG vs desmoglein 1+3	IgG vs BP180/BP230	IgA vs gluten/transglutaminase
Target	Desmosomes	Hemidesmosomes	Anchoring fibrils (reticulin)
Blister level	Suprabasal (intraepidermal)	Subepidermal	Subepidermal
Type	Flaccid; rupture easily	Tense; intact	Small itchy vesicles
Mucosa	Yes (scalp, face, axilla)	No (usually)	No
Nikolsky	Positive	Negative	Negative
DIF	Fishnet IgG (intercellular)	Linear IgG + C3 at BM	Granular IgA at dermal papillae
Association	—	—	Celiac disease

💡 High-yield: Pemphigus vulgaris = IgG vs desmoglein 1/3 (desmosomes), suprabasal/intraepidermal flaccid bullae, + mucosa, Nikolsky⁺, fishnet IgG on DIF. Bullous pemphigoid = IgG vs BP180/BP230 (hemidesmosomes), subepidermal tense bullae, no mucosa, linear IgG + C3 on DIF. Dermatitis herpetiformis = IgA vs gluten/transglutaminase, celiac disease association, extremely itchy subepidermal vesicles on extensor surfaces, granular IgA at dermal papillae (pathognomonic); Tx gluten-free diet + dapsone.